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  • 1
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In this paper data are presented indicating that immunotherapy with monoclonal anti-idiotypic antibodies (MoAb anti-id) can provoke different responses in the B-cell tumour concerned. With respect to the course of disease during and after immunotherapy, the in vitro findings may very well explain the in vivo observations in the two patients (D.E.F. B.O.R.) with B-cell chronic lymphocytic leukaemia (B-CLL) who were treated with MoAb anti-id. After initial tumour reduction, there was a recurrence of tumour cells with altered functional and phenotypic properties. In both cases the recurring tumour cells still expressed the same idiotype.In one patient (D.E.F.) the phenotypic changes (a surface Ig change from IgM, IgG, IgA, and IgD to weakly positive IgM and IgD) and functional changes (a 10-fold increase in [3H]thymidine uptake and a decreased idiotype secretion in vitro), together with the in vivo findings with respect to the course of disease–at relapse an impressive tumour regrowth rate with constant serum idiotype level–suggest that immunoselection might have taken place favouring the survival and relapse of a less mature, more aggressive tumour cell population with a lower idiotype expression.In the second patient (B.O.R.), the phenotypic changes (an isotype change from IgM and IgD to IgM with the loss of IgD, and a gradual decrease in expression of CD 19 and CD24) and functional changes (a 10-fold increase of idiotype secretion in vitro), together with the in vivo finding that the serum idiotype level had increased 25-fold compared with the preimmunotherapy serum level with comparable tumour load, strongly suggest an immunotherapy-induced differentiation of the malignant B cell.We also describe an increased expression of CD74, detected by MoAb BoM22, on the recurring tumour cells of patient B.O.R. whereas the expression of HLA-DP, -DQ and -DR did not change. The significance of this finding is unclear.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Annals of the New York Academy of Sciences 254 (1975), S. 0 
    ISSN: 1749-6632
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Natural Sciences in General
    Type of Medium: Electronic Resource
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  • 3
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 35 (1992), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We studied the distribution of Fcγ RIII (CD16) in human lymphoid and non-lymphoid tissue by immunohistochemistry and two-colour immunofluorescence. In all tissues except stomach, skin, muscle and heart, infiltrating cells were stained. In tonsil and thymus, the CDI6 antibody CLBgran I labelled some cells with high endothelial morphology in T-cell areas. Two-colour fluorescence combination of CD 16 and antibody to Von Willebrand factor confirmed the endothelial nature of the CLBgran l-positive cells. FcγRIII expression was also demonstrated by antibody CLBgran 11, which detects a product of the FcγRIII-B gene of only the NAI haplotype. A series of 95 endomyocardial biopsies (FMB) taken after heart transplantation was evaluated for FcγRIII expression. In 18 eases FcγRIII was unambiguously detected on endothelial cells by CD16 antibody CLBgranI. There was a significant correlation between capillary CD16 expression and transplant rejection. We conclude that FcγR expression on endothelium represents endothelial activation found in immunopathological and inflammatory conditions.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 27 (1988), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In the context of ex vivo T cell elimination from bone marrow, the anti-T cell cytotoxic potential of immunotoxins (IT) prepared by conjugation of die monoclonal antibodies (MOAb) WT32 (CD3), T101 (CD5), and WT1 (CD7) to ricin A chaw was evaluated. The cytotoxicity of IT was based on protein synthesis inhibition in human T cell lines: GHI, CEM, HPB-ALL, and Jurkat, and appeared closely related to the antigen density and internalization rate of the IT. Normal unstimulated T cells appeared to he rather insensitive to IT not due to a low antigen density or decreased internalization. The cytotoxicity of IT to T cells could he enhanced considerably by NH4Cl. Treatment of T cells with a cocktail of IT (10−8m) and 20 mm NH4Cl resulted in a 5000-fold cytoreduction as measured by clonogenic assays of limiting T cell dilutions, whereas the haematopoietic progenitor cells remained unaltered. Stimulation of T cells with phytobaemag-glutinin (PHA) prior to incubation with IT considerably increased the sensitivity to IT treatment. Thus, normal T cells are less sensitive to anti-T cell IT than T cell lines and activated T cells. This suggests that a low protein synthesis is responsible for the resistance to IT. However, a high specific cytotoxicity of IT to normal T cells can be achieved in the presence of 20 mm ammonium chloride.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 33 (1991), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Interleukin 6 (IL-6) is a cytokine with multiple biological activities on various tissues and cells. We have investigated the effect of recombinant human IL-6 (rhlL-6) on growth and differentiation of U937. Recombinant human IL-6 induced a dose-dependent growth inhibition, apparent around day 4, of up to 50% by day 8 of culture. Concomitant with this, changes in cytochemical activities were observed, indicative or differentiation. A panel of U937 antigens was analysed after culture with rhIL-6. Expression of the majority of these membrane antigens was unaffected, with the exception of two classes. First, rhIL-6 had a profound effect on members of the leucocytic cell adhesion molecules (Leu-CAM) family. Expression of the α-chain of CR3 (complement receptor 3; CD11b) was enhanced in a dose-dependent fashion, with maximal expression around day 7. Parallel to this a simultaneous increase in β-chain (CD18) expression was found. Furthermore, enhanced expression of CR3 was, accompanied by increased rosetting with sheep erythrocytes sensitized with C3bi. A much lower, but significant, enhancement was observed for the α-chain of the p150,95 antigen (CD11c). Expression of leucocyte function-associated antigen-1, (LFA-1), (CD11a/CD18) remained unchanged. Remarkably, however, expression of a ligand of LFA-1, intercellular adhesion molecule-1 (ICAM-1; CD54), was enhanced with similar kinetics as CR3 and p150,95. A specific anti-rhlL-6 antiserum completely inhibited the IL-6 effect. These observations provide further support for an important role of IL-6 in the regulation of myeloid cell development in man.
    Type of Medium: Electronic Resource
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  • 6
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Graft-versus-host disease (GVHD) after allogeneic hone marrow transplantation (BMT) is initiated by immunocompetent T fells present in the graft. Selective elimination of distinct T-cell subsets or a sufficient, but not complete T-cell depletion, might abolish severe GVHD without graft rejection and loss of the anti-tumour potential. In this study we analysed the efficacy of different monoclonal antibodies (MoAb) WT32(CD3), OKT4(CD4), T101 (CDS), WT1 (CD7), and WT82 (CD8) with respect to their cytotoxicity to T cells cither as immunotoxin (IT) or in combination with complement. The cytotoxic potential was assessed by protein synthesis inhibition and clonogenic a minor effect on blood or bone marrow T cells, although they were highly inhibitory to T-cell lines. However, in the presence of 20 mm ammonium chloride, IT directed against CD3, CDS, and CD7 were highly cytotoxic. IT directed against CD4 and CD8 were less effective, due to a low internalization. The complement-mediated cytotoxicity was efficient for all antigens used.The natural killer (NK) activity, as measured by cytotoxicity to K562, was hardly depressed by anti-CD3, anti-CD4, anti-CD5, and anti-CD8, but was eliminated by ami-CD7. All procedures used had only a minimal effect on haematopoietic progenitors as measured by CFU-GM and BFU-E assays. We concluded that, although the T-cell population can be eliminated with the combination of anti-CD3, anti-CD5, and anti-CD7 antibodies plus complement, IT with 20 mm NH4CI appear to kill higher amounts of T cells- Selective elimination of CD4- and CD8-positive cells is effectively obtained by MoAb with complement.
    Type of Medium: Electronic Resource
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  • 7
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: We have previously reported a polymorphism in the mitogenic effect of murine (m) IgG1 anti-CD3 monoclonal antibodies. This polymorphism was genetically determined and could be attributed to polymorphism of the Fc receptor (FcR) for mIgG1 present on human monocytes. We have now extended these studies by quantitating FcR expression on monocytes and cell lines by a recently developed EA rosette assay, using the erythrocyte-associated pseudoperoxidase activity. The data show that the polymorphism of the monocyte FcR for mIgG1 is based on a quantitative rather than an absolute difference. Furthermore, this FcR is specific for mIgG1 and does not bind mIgG2a or mIgG2b nor, surprisingly, human IgG. The expression of this FcR on cell lines correlates with their accessory function in IgG1 anti-CD3-induced T cell proliferation. mIgG2a can inhibit the rosetting of monocytes with erythrocytes sensitized with human IgG. The FcR detected by this rosette technique can interact with all four human IgG subclasses but not with mIgG1 or mIgG2b. The expression of this type of FcR on human cell lines correlates well with their ability to support mIgG2a anti-CD3-induced mitogenesis. These direct measurements of FcR expression support the concept that human monocytes have two independent FcR with affinity for mouse IgG: one receptor specigic for mIgG2a (which also binds human IgG), and a second specific for mIgG1.
    Type of Medium: Electronic Resource
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  • 8
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 28 (1988), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Anti-Ig antibodies can have two opposing effects on B-cell proliferation, resulting either in stimulation or inhibition. We have examined the proliferative response of 30 B-cell tumours to anti-Ig in the presence of absence of B-cell growth factor. Three reaction patterns were observed. In 12 cases a dose-dependent synergism between anti-Ig and B-cell growth factor was present in the induction of proliferation, in ten cases anti-Ig did not induce any response, and in eight cases anti-Ig suppressed the B-cell growth factor (BCGF)-induced proliferation. Similar responses to anti-Ig were found in the absence of BCGF. When these B-cell tumours were typed for expression of Ig isotypes, HLA class II antigens, several B-cell markers, activation markers, complement receptors, Fc receptors, cell size, and cell cycle phase, no correlation could be found with the proliferate response of these tumour B cells to anti-Ig. T cells or T-cell factors were not involved, because T-cell depletion did not change they tumour B-cell proliferative response to incubation with anti-Ig. The observed inhibition of proliferation did not correlate with the expression of Fc receptors, indicating the involvement of suppressor mechanisms other than the cross linking of Fc receptors with surface immunoglobulins. Tumour B cells, for which monoclonal anti-idiotypic antibodies (MoAb anti-id) were available, responded to MoAb anti-id in the same way as they did to anti-Ig. In view of the treatment of B-cell malignancies with MoAb anti-id, the question of whether these responses in vitro correlate with in vivo clinical outcome of anti-id therapy is of interest. So far our data show that the proliferative response of B-cell tumours to anti-Ig or MoAb anti-id is heterogeneous and cannot be linked to phenotype, is T cell-independent, and is most likely an intrinsic property of the malignant cell.
    Type of Medium: Electronic Resource
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  • 9
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Publishing Ltd
    Scandinavian journal of immunology 22 (1985), S. 0 
    ISSN: 1365-3083
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: The Raji-cell test is one of the most widely used methods for the detection and quantitation of immune complexes. Immune complexes and not 7 S IgG bind via C3 to complement receptors on the cell membrane of the Raji cell. During sucrose gradient fractionation of human and murine systemic lupus erythematosus sera, with a high Raji cell-binding activity, we could not demonstrate immune complexes in these sera. Subsequent analysis showed that the major part of the Raji cell binding was used by 7 S IgG with an anti-DNA specificity. Blocking experiments wilh complement-bearing aggregated IgG revealed that complement and Fc receptors were not involved in the binding of these anti-DNA antibodies to Raji cells. We conclude that the Raji cell test is not suitable for the detection and quantitation of immune complexes in sera containing anti-DNA antibodies.
    Type of Medium: Electronic Resource
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  • 10
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] When mononuclear cells from six healthy unrelated volunteers were testedfor the mitogenic effect of the monoclonal antibodies OKT 3, anti-Leu 4, UCHT1, WT 31, and WT 32, we found that WT 32 and OKT 3 were mitogenic for the lymphocytes from all six subjects. WT 31, anti-Leu 4, and UCHT1, however, ...
    Type of Medium: Electronic Resource
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